ROCHE INSTITUTE OF MOLECULAR BIOLOGY 
N UTLEY, NEW JERSEY 07110 
August 16, 1978 
Dr. Donald Fredrickson 
Director 
National Institutes of Health 
Bethesda, Maryland 20016 
Dear Dr. Fredrickson: 
I have received a copy of the Proposed Revised Guidelines for Recombinant 
DNA Research (Federal Register 43, 33042-33178) . While I am in agreement 
with almost all the RAC proposed revisions and their reasons for them, I 
would like to question the following: 
The proposed containment for shotgun recombinant DNA work on non-primate 
mammals and birds is P2 + EK2, yet for cold-blooded animals, plants and 
many of the RNA and DNA viruses it is P2 + EK2 or P3 + EK1. Is there a 
sound scientific basis for not also allowing non-primate and bird recombi- 
nant DNA work to be also carried out under P3 + EK1? The restriction to 
the use of only P2 + EK2 is not a trivial point, since many experiments 
using EK1 vectors are extremely difficult, indeed some simply impossible 
(e.g., those involving lysogenic X systems) in an EK2 system. In particu- 
lar, I find it difficult to see why segments of some transforming viruses 
may be cloned under P3 + EK.1 conditions, yet DNA from a non-primate mammal 
or bird in which any one sequence is diluted out at least one in 10^ with 
the other sequences present cannot be carried out under these same conditions. 
I would appreciate it if you could bring to the attention of the Advisory 
Committee this suggestion, i.e., allowing non-primate and bird shotgun 
DNA experiments at P2 + EK3 or P3 + EKL levels. 
Yours sincerely. 
Department of Cell Biology 
JM:SK 
[A-20] 
